研发双模式路易斯酸催化的分子内Prins/Conia-ene串联环化反应及其在天然产物全合成中的应用

双模式路易斯酸对发展串联反应是十分有用的，因为它们能通过两种配位模式（即σ和 π配位模式）来活化底物和反应中间体，进而诱导串联环化反应的发生。本课题组一直致力研发新型的双模式路易斯酸催化串联环化反应，能快速地构建多种多环体系，并应用于天然产物的全合成研究。我们最近研发出一种基于双模式路易斯酸的分子间Prins/Conia-ene串联环化反应，能以简单的原料，在“一锅煮”的条件下快速地构建1-氧杂环系，并应用于Phomactin A的合成。因此，本课题的目标是基于这种新的策略，发展分子内双模式路易斯酸催化的Prins/Conia-ene串联环化反应，以易得的关环底物为原料，在双模式路易斯酸的作用下，“一锅煮”的快速地构建5或6元环并8-氧杂二环[3.2.1]辛烷的三环骨架，并应用于Cortistatin A/J、Corianlactone和1,8-Epoxyosmitopsin的不对称合成。

Dual-mode Lewis acids are useful for developing cascade cyclization reactions since they can induce reactions via activation of substrates as well as intermediates in two different modes, namely the σ- and π-binding modes. Our group has a long-standing interest in developing new dual-mode Lewis acid induced cascade cyclizations for construction of various polycyclic ring systems and explore their utilities in natural product syntheses. Recently, we have reported a dual-mode Lewis acid induced intermolecular Prins/Conia-ene cascade cyclization reaction, which can provide 1-oxadecalins in one-pot with simple substrates. We have also employed this reaction for the synthesis of Phomactin A. Based on this strategy, the objective of this project is to develop dual-mode Lewis acid catalyzed intramolecular Prins/Conia-ene cascade cyclization reaction for construction of 5- or 6-membered ring fused with 8-oxabicyclo[3.2.1]octane in one-pot with readily prepared cyclization precursors. This new cyclization reaction will be employed for the formal synthesis of Cortistatin A/J, and asymmetric synthesis of Corianlactone and 1,8-Epoxyosmitopsin.